Ji-Ho Lee

A polymorphism of MS4A2 (- 109T > C) encoding the beta-chain of the high-affinity immunoglobulin E receptor (FcepsilonR1beta) is associated with a susceptibility to aspirin-intolerant asthma.

Background and objective The MS4A2 gene, the β chain of the high‐affinity receptor for immunoglobulin (Ig)E, has previously been linked to atopy and asthma. The β‐chain of FcɛR1 enhances receptor maturation and signal transduction capacity, leading to the release of proinflammatory mediators and cytokines that can exacerbate the symptom of asthma. This study was performed to evaluate whether two genetic polymorphisms of the FcɛR1β gene (FcɛR1β−109T>C and FcɛR1β E237G) are associated with aspirin‐intolerant asthma (AIA).

Aspirin-exacerbated respiratory disease: an update.

Purpose of review The pathophysiology of aspirin-exacerbated respiratory disease (AERD) is not fully understood and diagnostic methods and so far, treatments for AERD have not been standardized. We summarize recent research into the pathological mechanisms of AERD, diagnostic methods, and treatments for AERD patients. Recent findings In AERD pathophysiology, not only the reduced expression of E prostanoid 2 but also the dysfunction of its pathway could be involved. Moreover, eosinophils of AERD patients could be directly activated by aspirin to produce prostaglandin D2. Platelet activations are well known to be involved in AERD; however, plasma markers do not change during aspirin challenge tests. Additionally, novel genetic polymorphisms, such as P2RY12 and dipeptidyl peptidase 10 gene, and epigenetic predispositions of AERD were found. In AERD diagnosis, bronchial and nasal aspirin challenges have been applied in addition to oral challenge. Serum periostin has been suggested as a potential biomarker for AERD. Apart from standard pharmacological treatment and aspirin desensitization, biologics, including omalizumab and mepolizumab, as well as CRTH2 antagonists have been suggested as promising therapies for AERD treatment. Summary AERD is usually associated with severe asthma phenotypes. AERD pathophysiology mainly involves the dysregulation of eicosanoid metabolisms, activations of effector cells, which could be influenced by genetic/epigenetic factors. Understanding the pathophysiology of AERD is key to improve the diagnostic methods and proper management of AERD patients.

Prevalence and Clinical Characteristics of Local Allergic Rhinitis to House Dust Mites

Local allergic rhinitis (LAR) is a localized nasal allergic response in the absence of systemic atopy. The aim of this study was to evaluate the prevalence and clinical characteristics of LAR in Korean rhinitis patients compared to allergic rhinitis (AR) and non-allergic rhinitis (NAR). A total of 304 rhinitis patients were enrolled from November 2014 to March 2016. A skin prick test, serum total and specific immunoglobulin E, and a nasal provocation test (NPT) with house dust mite (HDM) were performed on all patients. Subjects also documented changes in rhinitis symptoms before and after NPT. Seventy-four patients with nasal hyper-reactivity and 80 patients with subclinical allergy were excluded. AR was diagnosed in 69 (46.0%) patients, NAR in 75 (50.0%) patients, and LAR to HDM in 6 (4.0%) patients. The average medication score and disease duration of each group were 14.5 points and 77.6 months in AR, 12.1 point and 51.1 months in NAR, and 17.7 point and 106.0 months in LAR, respectively. There were no significant differences in the baseline nasal symptom score of the three groups. However, after NPT with HDM, the score of rhinitis, itching, and obstructive were 4.83±1.47 vs. 1.95±2.53, 3.00±2.10 vs. 1.45±2.06, and 5.50±1.38 vs. 2.57±2.84 in LAR and NAR, respectively (p<0.05). LAR patients had longer duration of disease and tended to be older and have higher medication score than other rhinitis patients.

A Retrospective Study of Clinical Response Predictors in Subcutaneous Allergen Immunotherapy With House Dust Mites for Allergic Rhinitis

Purpose House dust mites (HDM) are major allergens that cause allergic rhinitis (AR). Allergen-specific subcutaneous immunotherapy (SCIT) has been shown to be clinically beneficial in many clinical trials. Such trials, however, are not reflective of all patient populations. The aim of this study was to describe the efficacy and safety of SCIT in routine clinical practice in Korean adults with AR sensitized to HDM. Methods We reviewed medical records of 304 patients with AR treated at an allergy clinic of a tertiary hospital using SCIT with aluminum hydroxide-adsorbed allergen extract targeting HDM alone or with pollens for at least 1 year from 2000 to 2012. Patients with asthma were excluded. Rates of remission, defined as no further requirement of maintenance medication, over time were determined by means of life tables and extension of survival analysis. Specific immunoglobulin E (IgE) levels to HDM were categorized into 6 classes. Results The mean time until achieving remission was 4.9±0.1 years, and the cumulative incidence of remission from AR was 76.6%. Severe AR (odds ratio [OR], 0.40; 95% confidence interval [CI], 0.23-0.69; P=0.001), specific IgE levels to HDM ≥17.5 kU/L (OR, 1.85; 95% CI, 1.01-3.37; P=0.045), and duration of immunotherapy ≥3 years (OR, 7.37; 95% CI, 3.50-15.51; P<0.001) were identified as significant predictors of clinical remission during SCIT for patients with AR sensitized to HDM. Overall, 73 patients (24.0%) experienced adverse reactions to SCIT, and only 1 case of anaphylaxis (0.3%) developed. Conclusions SCIT with HDM was found to be effective and safe for patients with AR. Specific IgE levels to HDM and a duration of SCIT ≥3 years may be predictors of clinical responses to SCIT in AR patients.

Neutrophil Extracellular DNA Traps Induce Autoantigen Production by Airway Epithelial Cells

The hypothesis of autoimmune involvement in asthma has received much recent interest. Autoantibodies, such as anti-cytokeratin (CK) 18, anti-CK19, and anti-α-enolase antibodies, react with self-antigens and are found at high levels in the sera of patients with severe asthma (SA). However, the mechanisms underlying autoantibody production in SA have not been fully determined. The present study was conducted to demonstrate that neutrophil extracellular DNA traps (NETs), cytotoxic molecules released from neutrophils, are a key player in the stimulation of airway epithelial cells (AECs) to produce autoantigens. This study showed that NETs significantly increased the intracellular expression of tissue transglutaminase (tTG) but did not affect that of CK18 in AECs. NETs induced the extracellular release of both tTG and CK18 in a concentration-dependent manner. Moreover, NETs directly degraded intracellular α-enolase into small fragments. However, antibodies against neutrophil elastase (NE) or myeloperoxidase (MPO) attenuated the effects of NETs on AECs. Furthermore, each NET isolated from healthy controls (HC), nonsevere asthma (NSA), and SA had different characteristics. Taken together, these findings suggest that AECs exposed to NETs may exhibit higher autoantigen production, especially in SA. Therefore, targeting of NETs may represent a new therapy for neutrophilic asthma with a high level of autoantigens.

Leukotriene Receptor Antagonists for the Treatment of Asthma in Elderly Patients.

Elderly asthma (EA) is regarded as a distinct phenotype of asthma and is associated with age-related changes in airway structure and alterations in lung function and immune responses. EA is difficult to diagnose because of aging and co-morbidities, and overlaps with fixed airway obstructive disease. Novel modalities to differentiate between EA and chronic obstructive pulmonary disease (COPD) are necessary. A multifaceted approach, including clinical history, smoking habits, atopy, and measurement of lung function, is mandatory to differentiate asthma from COPD. There are a variety of co-morbidities with EA, of which COPD, upper airway diseases, depression, obesity, and hypertension are the most common, and these co-morbidities can affect the control status of EA. However, leukotriene receptor antagonists (LTRAs) can facilitate the management of EA, and thus addition of an LTRA to inhaled corticosteroid (ICS) monotherapy or ICS plus long-acting β2-agonist therapy improves symptoms in EA patients. LTRA treatment is safe and beneficial in patients who are unable to use inhalation devices properly or who have co-morbid diseases. Therefore, clinical studies targeting a specific population of EA patients are warranted to help achieve a better therapeutic strategy in EA patients.

Therapeutic Effect of Omalizumab in Severe Asthma: A Real-World Study in Korea

Purpose Omalizumab, an anti-immunoglobulin E (IgE) monoclonal antibody, has proved to be effective for the treatment of severe asthma. However, there is no direct evidence of effectiveness of omalizumab in Korean patients with severe asthma. We sought to evaluate the real-world effectiveness of omalizumab in Korean adult patients suffering from severe asthma and to identify predictors of favorable response. Methods A retrospective analysis of electrical medical records was performed on severe allergic asthmatic patients with omalizumab treatment group (OT group) for more than 6 months between March 2008 and February 2016. Propensity score matching was applied to define the standardized treatment control group (STC group) treated without omalizumab. Asthma-related outcomes were compared between the 2 groups, and analyzed before and after omalizumab use in the OT group. Responders to treatment were defined as patients showing >50% reduction in asthma exacerbations and/or systemic steroid requirement during the outcome period. Results One hundred twenty-four patients with severe asthma (62 in the OT group; 62 in the STC group) were enrolled in the study. Proportion of patients having the reduction of asthma exacerbation (53.2% vs 35.5%, P=0.015) and the rate of responders (67.7% vs 41.9%, P=0.007) were significantly higher in the OT group than in the STC group. Significant reductions were noted in asthma exacerbation (P=0.006), hospitalization (P=0.009), hospitalization days (P=0.006), systemic corticosteroid requirements (P=0.027), and sputum eosinophil count (P=0.031) in OT group compared with STC group. There were no significant differences in changes of forced expiratory volume in the 1 second (FEV1) levels between the 2 groups. No predictors of responders were found for omalizumab treatment. Conclusions Omalizumab can reduce exacerbations/hospitalization/systemic steroid burst in Korean adult patients with severe asthma.

An update on the management of aspirin-exacerbated respiratory disease

ABSTRACT Introduction: Clinical features of aspirin-exacerbated respiratory disease (AERD) consist of moderate to severe asthma associated with chronic rhinosinusitis (CRS), which are derived from overproduction of cysteinyl leukotrienes along with chronic type 2 mediated inflammation in the upper and lower airway mucosa. Area covered: This review provides recent up-to-date information regarding phenotypes of AERD and encompasses comprehensive diagnostic methods and treatment options. To confirm the diagnosis of AERD, provocation testing via nasal, inhalation or the oral route of aspirin remains the gold standard; in vitro diagnostic methods are still not available. Essential management is to avoid cross-reacting cyclooxygenase 1 (COX-1) inhibitors along with use of highly selective COX-2 inhibitors and to maintain pharmacologic treatment depending on the severity of asthma and chronic rhinosinusitis. Recent biologics, including anti-IgE and anti-IL5 antibodies, are required in severe AERD patients with CRS. Aspirin desensitization can be recommended when indicated. Expert commentary: AERD is a heterogeneous disease in terms of severity and associated allergic disease. When performing diagnosis and treatment for AERD, such disease characteristics need to be kept in mind.

Immunomodulatory function of surfactant protein D in eosinophilic asthma

1. Roberts G, Pfaar O, Akdis CA, et al. EAACI guidelines on allergen immunotherapy: allergic rhinoconjunctivitis. Allergy. 2017;73:765‐ 798. 2. Weinstein SF, Katial R, Jayawardena S, et al. Efficacy and safety of dupilumab in perennial allergic rhinitis and comorbid asthma. J Allergy Clin Immunol. 2018;114:171‐177. 3. Compalati E, Passalacqua G, Bonini M, Canonica GW. The efficacy of sublingual immunotherapy for house dust mites respiratory allergy: results of a GA2LEN meta‐analysis. Allergy. 2009;64:1570‐1579. 4. Yukselen A, Kendirli S, Yilmaz M, Altintas D, Karakoc G. Effect of one‐year subcutaneous and sublingual immunotherapy on clinical and laboratory parameters in children with rhinitis and asthma: a randomized, placebo‐controlled, double‐blind, double‐dummy study. Int Arch Allergy Immunol. 2012;157:288‐298. 5. Xu LZ, Yang LT, Qiu SQ, et al. Combination of specific allergen and probiotics induces specific regulatory B cells and enhances specific immunotherapy effect on allergic rhinitis. Oncotarget. 2016;7:54360‐ 54369. 6. Dhami S, Nurmatov U, Arasi S, et al. Allergen immunotherapy for allergic rhinoconjunctivitis: a systematic review and meta‐analysis. Allergy. 2017;72:1597‐1631. 7. Nelson H, Cartier S, Allen-Ramey F, Lawton S, Calderon MA. Network meta‐analysis shows commercialized subcutaneous and sublingual grass products have comparable efficacy. J Allergy Clin Immunol Pract. 2015;3:256‐266. 8. Di Bona D, Plaia A, Leto-Barone MS, La Piana S, Di Lorenzo G. Efficacy of subcutaneous and sublingual immunotherapy with grass allergens for seasonal allergic rhinitis: a meta‐analysis‐based comparison. J Allergy Clin Immunol. 2012;130:1097‐1107. 9. Durham SR, Penagos M. Sublingual or subcutaneous immunotherapy for allergic rhinitis? J Allergy Clin Immunol. 2016;137:339‐349. 10. Soh JY, Thalayasingam M, Ong S, Loo EX, Shek LP, Chao SS. Sublingual immunotherapy in patients with house dust mite allergic rhinitis: prospective study of clinical outcomes over a two‐year period. J Laryngol Otol. 2016;130:272‐277.

Propacetamol poses a potential harm of adverse hypotension in male and older patients: Propacetamol and Paracetamol-Associated Hypotension

Researchers recently suggested intravenous paracetamol as a potential cause of hypotension. We aimed to investigate risk factors of paracetamol‐ and propacetamol‐associated adverse drug reactions (ADRs) in Korean individuals.